全文获取类型
收费全文 | 502篇 |
免费 | 53篇 |
出版年
2022年 | 2篇 |
2021年 | 11篇 |
2020年 | 5篇 |
2019年 | 9篇 |
2018年 | 7篇 |
2017年 | 10篇 |
2016年 | 17篇 |
2015年 | 19篇 |
2014年 | 20篇 |
2013年 | 23篇 |
2012年 | 27篇 |
2011年 | 30篇 |
2010年 | 24篇 |
2009年 | 16篇 |
2008年 | 15篇 |
2007年 | 27篇 |
2006年 | 29篇 |
2005年 | 18篇 |
2004年 | 18篇 |
2003年 | 15篇 |
2002年 | 12篇 |
2001年 | 18篇 |
2000年 | 20篇 |
1999年 | 13篇 |
1998年 | 13篇 |
1997年 | 11篇 |
1996年 | 9篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 8篇 |
1990年 | 8篇 |
1989年 | 8篇 |
1988年 | 6篇 |
1987年 | 7篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1984年 | 7篇 |
1983年 | 7篇 |
1982年 | 7篇 |
1981年 | 3篇 |
1978年 | 4篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 5篇 |
1974年 | 6篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1933年 | 1篇 |
排序方式: 共有555条查询结果,搜索用时 15 毫秒
101.
Sicong Zhou Yueqi Lu Jiani Chen Zhongqiu Pan Lan Pang Ying Wang Qichao Zhang Michael R. Strand Xue-Xin Chen Jianhua Huang 《The ISME journal》2022,16(11):2574
Studying the microbial symbionts of eukaryotic hosts has revealed a range of interactions that benefit host biology. Most eukaryotes are also infected by parasites that adversely affect host biology for their own benefit. However, it is largely unclear whether the ability of parasites to develop in hosts also depends on host-associated symbionts, e.g., the gut microbiota. Here, we studied the parasitic wasp Leptopilina boulardi (Lb) and its host Drosophila melanogaster. Results showed that Lb successfully develops in conventional hosts (CN) with a gut microbiota but fails to develop in axenic hosts (AX) without a gut microbiota. We determined that developing Lb larvae consume fat body cells that store lipids. We also determined that much larger amounts of lipid accumulate in fat body cells of parasitized CN hosts than parasitized AX hosts. CN hosts parasitized by Lb exhibited large increases in the abundance of the bacterium Acetobacter pomorum in the gut, but did not affect the abundance of Lactobacillus fructivorans which is another common member of the host gut microbiota. However, AX hosts inoculated with A. pomorum and/or L. fructivorans did not rescue development of Lb. In contrast, AX larvae inoculated with A. pomorum plus other identified gut community members including a Bacillus sp. substantially rescued Lb development. Rescue was further associated with increased lipid accumulation in host fat body cells. Insulin-like peptides increased in brain neurosecretory cells of parasitized CN larvae. Lipid accumulation in the fat body of CN hosts was further associated with reduced Bmm lipase activity mediated by insulin/insulin-like growth factor signaling (IIS). Altogether, our results identify a previously unknown role for the gut microbiota in defining host permissiveness for a parasite. Our findings also identify a new paradigm for parasite manipulation of host metabolism that depends on insulin signaling and the gut microbiota.Subject terms: Animal physiology, Microbial ecology 相似文献
102.
Adult stem cells vary widely in their rates of proliferation. Some stem cells are constitutively active, while others divide only in response to injury. The mechanism controlling this differential proliferative set point is not well understood. The anterior-posterior (A/P) axis of the adult Drosophila midgut has a segmental organization, displaying physiological compartmentalization and region-specific epithelia. These distinct midgut regions are maintained by defined stem cell populations with unique division schedules, providing an excellent experimental model with which to investigate this question. Here, we focus on the quiescent gastric stem cells (GSSCs) of the acidic copper cell region (CCR), which exhibit the greatest period of latency between divisions of all characterized gut stem cells, to define the molecular basis of differential stem cell activity. Our molecular genetic analysis demonstrates that the mitogenic EGF signaling pathway is a limiting factor controlling GSSC proliferation. We find that under baseline conditions, when GSSCs are largely quiescent, the lowest levels of EGF ligands in the midgut are found in the CCR. However, acute epithelial injury by enteric pathogens leads to an increase in EGF ligand expression in the CCR and rapid expansion of the GSSC lineage. Thus, the unique proliferative set points for gut stem cells residing in physiologically distinct compartments are governed by regional control of niche signals along the A/P axis. 相似文献
103.
Sofia Kamlund Daniel Strand Birgit Janicke Kersti Alm 《Cell cycle (Georgetown, Tex.)》2017,16(21):2128-2138
Most studies on new cancer drugs are based on population-derived data, where the absence of response of a small population may pass unnoticed. Thus, individual longitudinal tracking of cells is important for the future development of efficient cancer treatments. We have used digital holographic microscopy to track individual JIMT-1 human breast cancer cells and L929 mouse fibroblast cultivated in normoxia or hypoxia. In addition, JIMT-1 cells were treated with salinomycin, a cancer stem cell targeting compound. Three-day time-lapse movies were captured and individual cells were analysed with respect to cell division (cell cycle length) and cell movement. Comparing population-doubling time derived from population-based growth curves and individual cell cycle time data from time-lapse movies show that the former hide a sub-population of dividing cells. Salinomycin treatment increased the motility of cells, however, this motility did not result in an increased distant migration i.e. the cells increased their local movement. MCF-7 breast cancer cells showed similar motility behaviour as salinomycin-treated JIMT-1 cells. We suggest that combining features, such as motility and migration, can be used to distinguish cancer cells with mesenchymal (JIMT-1) and epithelial (MCF-7) features. The data clearly emphasize the importance of longitudinal cell tracking to understand the biology of individual cells under different conditions. 相似文献
104.
105.
Allan E. Strand Brook G. Milligan Casey M. Pruitt 《Evolution; international journal of organic evolution》1996,50(5):1822-1829
The degree to which conspecific populations are interconnected via ongoing gene flow remains an important focus of evolutionary biology. One major difficulty in distinguishing ongoing gene flow from historical subdivision is that either process can generate similar estimates of apparent gene flow. Thus, gene flow estimates themselves are insufficient to distinguish between these alternatives. However, genetic data coupled with additional information about demography and distribution do allow a distinction to be made. Here we address the specific question, does gene flow link populations of Aquilegia? In a survey of a 525 B.P. chloroplast DNA fragment sampled from 251 individual plants from 18 populations of three taxa, five haplotypes were identified. No significant relationship between geographic distance and apparent gene flow between population pairs existed. Further, the estimated level of gene flow was entirely compatible with a historical subdivision of Aquilegia populations during the late Pleistocene or early Holocene. Therefore, these patterns of variation are due not to ongoing gene flow, but rather to historical association among populations. Thus Aquilegia populations may be considered as distinct evolutionary entities with regard to seed-mediated processes. As a result, comparative analysis of ecological traits undergoing potentially rapid evolution (e.g., life histories, mating systems, inbreeding depression) should be possible in these taxa. 相似文献
106.
Shoots of cold-acclimated seedlings of Pinus sylvestris L. were exposed to a temperature of –7°C for 4 h, in darkness or at a photon flux density of 1 300 μmol m-2 s-1 . Before and after freezing, fluorescence kinetics of intact needles and isolated chloroplast membranes were measured at both room temperature and 77 K. Maximum and variable fluorescence yield of photosystem II both at room temperature and 77 K decreased strongly after freezing in light, whereas the initial fluorescence yield was little affected. Quenching of maximum and variable fluorescence of photosystem I at 77 K also occurred. The results show that freezing in light damages photosystem II, thereby increasing the radiationless decay at the reaction centres of photosystem II. This is a typical symptom of photoinhibition of photosynthesis. Freezing in darkness did not significantly reduce fluorescence yield of photosystem II or photosystem I. Moreover, electron transport capacity was not significantly affected. We therefore suggest that the inhibition of the CO2 assimilation in pine seedlings by freezing alone does not involve thylakoid inactivation. 相似文献
107.
108.
Induction of protective immunity in mice using a 62-kDa recombinant fragment of a Schistosoma mansoni surface antigen. 总被引:13,自引:0,他引:13
L M Soisson C P Masterson T D Tom M T McNally G H Lowell M Strand 《Journal of immunology (Baltimore, Md. : 1950)》1992,149(11):3612-3620
Mice exposed to radiation-attenuated cercariae of Schistosoma mansoni are highly resistant to challenge infection, and sera from these mice can confer partial resistance when transferred to naive recipients. These sera recognize Ag present in schistosomular and adult worms, among them an Ag of 200 kDa. A cDNA encoding a 62-kDa portion of this Ag was cloned; the deduced amino acid sequence of this cDNA clone shares homology with myosins of other species. To assess the immunoprophylactic potential, we carried out vaccination trials in mice using the recombinant polypeptide expressed as a fusion protein with beta-galactosidase presented in the form of proteosome complexes with the outer membrane protein of meningococcus. The level of protection achieved was 32%, and this level could be increased to 75% by removal of those amino acids included in the fusion protein that were derived from the vector to yield a polypeptide, designated rIrV-5. A similar level of protection was achieved when mice were immunized with the same dose of rIrV-5 in the form of protein complexes but without outer membrane protein, suggesting that protection did not require the use of adjuvant. However, at least three immunizations were necessary to achieve protection. Using mAb and sera from mice vaccinated with rIrV-5, we demonstrated that the native protein recognized by antibodies against rIrV-5 is a 200-kDa protein that is expressed on the surface of newly transformed schistosomula. The protection achieved with rIrV-5 in mice encourages additional studies of its potential as a vaccine candidate for the prevention of schistosomiasis. 相似文献
109.
Vibeke Strand Evo Alemao Thomas Lehman Alyssa Johnsen Subhashis Banerjee Harris A. Ahmad Philip J. Mease 《Arthritis research & therapy》2018,20(1):269
Background
To explore the effect of abatacept treatment on patient-reported outcomes (PROs) in psoriatic arthritis (PsA).Methods
Patients with PsA were randomised (1:1) to subcutaneous abatacept 125?mg weekly/placebo for 24?weeks with early escape (EE) to open-label abatacept (week 16). Adjusted mean changes from baseline to weeks 16 (all patients) and 24 (non-EE responders) in Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form-36 (SF-36; physical and mental component summary and domains), Dermatology Life Quality Index and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated. Subpopulations were analysed by baseline C-reactive protein (CRP) level (> vs?≤?upper limit of normal [ULN]) and prior tumour necrosis factor inhibitor (TNFi) exposure. Proportions of patients reporting improvements ≥ minimal clinically important differences (MCIDs) and?≥?normative values (NVs) in HAQ-DI, SF-36 and FACIT-F (week 16 before EE) were analysed.Results
In total population, numerically higher improvements in most PROs were reported with abatacept (n?=?213) versus placebo (n?=?211) at both time points (P?>?0.05). Higher proportions of abatacept versus placebo patients reported PRO improvements ≥ MCID and?≥?NV at week 16. At week 16, all PRO improvements were numerically greater (P?>?0.05) in patients with baseline CRP?>?ULN versus CRP?≤?ULN (all significant [95% confidence interval] for abatacept vs placebo); improvements in SF-36 component summaries and FACIT-F were greater in TNFi-naïve versus TNFi-exposed patients (abatacept > placebo). Week 24 subgroup data were difficult to interpret due to low patient numbers.Conclusions
Abatacept treatment improved PROs in patients with PsA versus placebo, with better results in elevated baseline CRP and TNFi-naïve subpopulations.Trial registration
ClinicalTrials.gov number, NCT01860976 (funded by Bristol-Myers Squibb); date of registration: 23 May 2013.110.